Patent Documents 1 and 2 disclose a 10-(3-cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl)pyridobenzoxazine carboxylic acid derivative and a 7-(3-cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl)quinolone carboxylic acid derivative as antibacterial agents which show excellent antibacterial activities on resistant bacteria and are highly safe.
Patent Documents 1 and 2 disclose a method for producing (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine which is a useful intermediate, but, the synthetic pathway thereof requires nine steps from N-methoxymethyl-N-(trimethylsilylmethyl)benzylamine as a starting material, through a fluorination of 3-azidomethyl-4-hydroxypyrrolidine, to a synthesis of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine.
Patent Documents 3 and 4 also disclose improved methods for preparation of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine.
The method disclosed in Patent Document 3 is a synthesis method in which a fluorinating agent is allowed to react with a 3-bromomethyl-4-hydroxypyrrolidine derivative, and which is led to a 3-bromomethyl-4-fluoropyrrolidine derivative, and then, a cyclopropylamino group is introduced. However, in the method disclosed in Patent Document 3, all intermediates are oily products and are difficult to purify.
In Patent Document 4, a synthesis method for (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine using asymmetric hydrogenation is disclosed. In Patent Document 4, introduction of a fluorine group is carried out on a 1-protected-3-(N-protected-N-cyclopropyl)aminomethyl-4-hydroxypyrrolidine derivative using perfluoro-1-octanesulfonyl fluoride. In this case, an aralkyl group such as a benzyl group, an aralkoxycarbonyl group such as a benzyloxycarbonyl group, or an alkoxycarbonyl group such as a tert-butyloxycarbonyl group is used as a protecting group for a cyclopropylamino group.
That is, in Patent Document 4, a fluorination of a 1-protected-3-(N-protected-N-cyclopropyl)aminomethyl-4-hydroxypyrrolidine derivative shown in following scheme 1 is shown as the synthesis method for syn-3-(N-substituted-aminomethyl)-4-fluoropyrrolidines.

In general formulae (1) and (2), PG1 represents a protecting group for an amino group, PG2 represents an aralkyl group, an aralkoxycarbonyl group, an alkoxycarbonyl group, or an acyl group.
Meanwhile, a method for producing a fluoroamine from an amino alcohol is classified into a method in which after an amino group is protected once, a hydroxyl group is fluorinated and a protecting group for the amino group is deprotected, and a method in which a hydroxyl group is directly fluorinated with an amino group being unprotected.
As the method in which after an amino group is protected once, a hydroxyl group is fluorinated and the amino group is deprotected, examples in which a fluorination reaction is carried out with protecting the amino group with an alkoxycarbonyl group such as a tert-butyloxycarbonyl group (Patent Document 5 and Non-Patent Documents 1 and 2). In addition, Non-Patent Document 6 discloses a fluorination of a N-(2-nitrobenzenesulfonyl)amino alcohol derivative of which an amino group is protected with a 2-nitrobenzenesulfonyl group.
As the prior art in which a fluorination of a hydroxyl group is carried out with an amino group of an amino alcohol being unprotected, a method in which a hydrogen fluoride-pyridine complex is used (Non-Patent Document 3), a method in which a sulfur tetrafluoride derivative is used (Patent Document 6), and a method in which sulfur tetrafluoride and liquid hydrogen fluoride are used (Non-Patent Documents 4 and 5) have been reported.
In the method of Non-Patent Document 3, the yield is relatively satisfactory, however, there is a problem that it takes several days to complete the reaction. In addition, in Patent Document 6, an N-benzyl-N-(2-hydroxyethyl)amine derivative is converted to an N-benzyl-N-(2-fluoroethyl)amine derivative using DAST which is a sulfur tetrafluoride derivative, however, a yield thereof is as low as 17%.
In Non-Patent Documents 4 and 5, a fluorinated amine is obtained from reacting sulfur tetrafluoride in liquid hydrogen fluoride at −78° C., however, a rearrangement of the fluorinated position occurs. That is, when 3-hydroxypiperidine is used, the yield of 3-fluoropiperidine which is the target compound, is reduced since 4-fluoropiperidine which is a positional isomer is formed.